Abstract
The transcription factor Pax5 is essential for initiating B cell lineage commitment, but its role in maintaining commitment is unknown. Using conditional Pax5 inactivation in committed pro-B cells, we demonstrate that Pax5 is required not only to initiate its B lymphoid transcription program, but also to maintain it in early B cell development. As a consequence of Pax5 inactivation, previously committed pro-B cells regained the capacity to differentiate into macrophages in vitro and to reconstitute T cell development in vivo in RAG2-/- mice. Hence, Pax5 expression is continuously required to maintain B cell lineage commitment, because its loss converts committed pro-B cells into hematopoietic progenitors with multilineage potential.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Antigens, CD19 / genetics
-
Antigens, CD19 / metabolism
-
B-Lymphocytes / cytology
-
B-Lymphocytes / physiology*
-
Cell Differentiation
-
Cell Lineage
-
Cells, Cultured
-
DNA-Binding Proteins / genetics*
-
DNA-Binding Proteins / metabolism*
-
Gene Expression Profiling
-
Gene Expression Regulation
-
Gene Silencing
-
Hematopoietic Stem Cells / cytology
-
Hematopoietic Stem Cells / physiology*
-
Macrophages / cytology
-
Macrophages / physiology
-
Mice
-
Mice, Inbred C57BL
-
Mice, Transgenic
-
PAX5 Transcription Factor
-
T-Lymphocytes / cytology
-
T-Lymphocytes / physiology
-
Tamoxifen / analogs & derivatives*
-
Tamoxifen / pharmacology
-
Transcription Factors / genetics*
-
Transcription Factors / metabolism*
-
Transcription, Genetic
Substances
-
Antigens, CD19
-
DNA-Binding Proteins
-
PAX5 Transcription Factor
-
Pax5 protein, mouse
-
Transcription Factors
-
Tamoxifen
-
afimoxifene